Molecular Biology of Valvular Heart Disease

1. Front Matter

   Pages i-xvii

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2. Calcific Aortic Valve Disease: The Role of the Stem Cell Niche

   • Nalini M. Rajamannan, Christopher M. Johnson

   Pages 1-12

3. In Vitro Cell Culture Model of Calcification: Molecular Regulation of Myofibroblast Differentiation to an Osteoblast Phenotype

   • Nalini M. Rajamannan, Muzaffer Cicek, John R. Hawse, Thomas C. Spelsberg, Malayannan Subramaniam

   Pages 13-20

4. Aortic Valve Apoptosis, Cell Proliferation and Atherosclerosis in Experimental Hypercholesterolemia

   • Mony Shuvy, Chaim Lotan, Nalini M. Rajamannan

   Pages 21-25

5. Experimental Model of Aortic Valve Calcification to Induce Osteoblast Differentiation

   • Nalini M. Rajamannan, Muzaffer Cicek, John R. Hawse, Thomas C. Spelsberg, Malayannan Subramaniam

   Pages 27-33

6. Development of an Experimental Model of Mitral Valve Regurgitation via Hypertrophic Chondrocytes

   • Nalini M. Rajamannan, Jeff Park, Francesco Antonini-Canterin

   Pages 35-40

7. Testing Drug Eluting Paclitaxel Balloon Valvuloplasty in an Experimental Model of Aortic Stenosis

   • Konstantinos Spargias, Mariann Gyöngyösi, Rayyan Hemetsberger, Aniko Posa, Noemi Pavo, Imre J. Pavo et al.

   Pages 41-47

8. Ex Vivo Model for Bioprosthetic Valve Calcification via Stem Cell Differentiation to Bone

   • Nalini M. Rajamannan

   Pages 49-54

9. Experimental Hypercholesterolemia in Genetic ApoE−/−/Lrp5−/− Mice: Proof of Principle

   • Nalini M. Rajamannan

   Pages 55-60

10. Wnt3a-Lrp5 mediated Bicuspid Aortic Valve Disease

    • Nalini M. Rajamannan

    Pages 61-65

11. Mouse Models of Calcific Aortic Valve Disease

    • Bin Zhang, Grace Casaclang-Verzosa, Jordan D. Miller

    Pages 67-80

12. Hemodynamic Mechanisms of Bicuspid Aortic Valve Calcification and Aortopathy

    • Philippe Sucosky

    Pages 81-94

13. Bioreactor and Biomaterial Platforms for Investigation of Mitral Valve Biomechanics and Mechanobiology

    • Patrick S. Connell, Varun K. Krishnamurthy, K. Jane Grande-Allen

    Pages 95-106

14. Identification of Early Pathological Events in Calcific Aortic Valve Disease by Molecular Imaging

    • Eduardo Martínez-Martínez, Elena Aikawa

    Pages 107-116

15. Role of Ectonucleotidases and Purinergic Receptors in Calcific Aortic Valve Disease

    • Patrick Mathieu, Ablajan Mahmut, Philippe Pibarot, Yohan Bossé, Marie-Chloé Boulanger

    Pages 117-126

16. In Vitro Model of Drug Testing

    • Nalini M. Rajamannan

    Pages 127-130

17. Application of the LDL-Density-Pressure Theory: The Mitral Valve

    • Nalini M. Rajamannan

    Pages 131-138

18. Application of the LDL-Density-Radius Theory: The Aortic Valve

    • Nalini M. Rajamannan, Francesco Antonini-Canterin, Kristian Wachtal

    Pages 139-146

19. Back Matter

    Pages 147-150

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The cellular mechanisms of valvular heart disease have not been elucidated until the last decade. To date, there is no medical therapy that is FDA or CE mark approved for the treatment and/or slowing the progression of this disease. This textbook will provide the cellular basis for medical therapy. Over the past decade, research laboratories are more and more evolving into valvular biology programs from the traditional vascular biology. The science between the two disciplines, although has several similarities has unique cellular targets secondary to the embryologic derivation of the heart valve  and the hemodynamics involved in the understanding of this disorders. This textbook will be a natural progression from the recently published text Cardiac Valvular Medicine, Springer 2012. This new textbook will provide the cellular details and the more basic molecular biology approaches towards understanding the disease, providing novel cellular targets and finally developing future clinical trials in the medical treatment of valvular heart disease in the future.

• Aortic valve disease
• Bioprosthetic valve calcification
• Cardiac Valves
• Elastin Biology of the cardiac valve
• Mitral valve disease
• TAVI

• Biochemistry & Molecular Biology Dept., Mayo Clinic, Rochester, USA

  Nalini M. Rajamannan

Nalini M. Rajamannan, MD has been studying the cellular biology of valvular heart disease since 1987. She has trained at the Mayo Clinic, in molecular biology, cardiology and echocardiography to develop an expertise which is translational in the approach towards valvular medicine. Her expertise has developed the initial experimental models towards studying medical therapies for this disease process. She is the chair of NHLBI/NIH working group in calcific aortic valve disease. This white paper was published in Circulation in Oct 2011. She has had NIH funding in this field since 2002 and has published 60 papers, several book chapters and the most recent textbook in Cardiac Valvular Medicine. She also has 3 patents in the field of cardiac valve signaling and pathogenesis of this disease.

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